Mixing apparatus and method

ABSTRACT

Apparatus for mixing a number of components comprising a vessel for receiving the components, drive means for rotating or oscillating the vessel about an axis to effect mixing of the components within the vessel, and at least one spectroscopic monitoring means for repeatedly scanning the mixture to obtain data for use in monitoring changes in the spectroscopic profile of the mixture as mixing proceeds, the monitoring means by mounted off-axis relative to the axis about which the vessel is rotatable or oscillatable.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 09/784,081, filedFeb. 16, 2001, now U.S. Pat. No. 6,517,230, issued Feb. 11, 2003, andwhich further claims priority from U.S. Provisional Ser. No. 60/186,759,filed Mar. 3, 2000. These applications in their entirety areincorporated herein by reference.

This invention relates to apparatus for and a method of mixingcomponents, for example to effect blending of components to form ahomogeneous mixture. The components will usually be in the form ofpowders but the invention is also applicable to the mixing of otherfluent components such as liquids. Typically the components to be mixedcomprise pharmaceutical actives and excipients prior to furtherprocessing thereof, e.g. tableting.

The production of homogeneous mixtures of actives and excipients is ofparticular importance in the pharmaceutical industry.

EP-A-0631810 discloses that in-line monitoring of the degree ofhomogeneity achieved in the course of blending components such aspharmaceutical actives and excipients is possible by detecting thespectroscopic characteristics of the mixture during the blendingprocess. Where the blending process is carried out by means of arotating mixing vessel, EP-A-0631810 teaches that the device forprojecting radiation into and receiving reflected radiation from themixture is associated with a shaft about which the vessel, specificallya V-blender, is rotated. This arrangement results in the device beinglocated invasively with respect to the interior of the mixing vessel.The reflected radiation is conveyed to spectroscopic means located inthe vicinity of the rotating mixing vessel for storage and analysis bythe spectroscopic means or by a separate data acquisition and a controlcomputer linked to the spectroscopic means.

The present invention seeks to provide improved in-line spectroscopicmonitoring of mixing, especially but not exclusively blending, processeswhich may be non-invasive while affording greater freedom in terms ofsiting relative to the mixing zone.

According to one aspect of the present invention there is providedapparatus for mixing a number of components comprising a vessel forreceiving the components, drive means for rotating or oscillating thevessel about an axis to effect mixing of the components within thevessel, and at least one spectroscopic monitoring means for repeatedlyscanning the mixture to obtain data for use in monitoring changes in thespectroscopic profile of the mixture as mixing proceeds, the monitoringmeans being mounted off-axis relative to the axis about which the vesselis rotatable or oscillatable.

The monitoring means may be provided directly on-board the vessel or mayinstead be provided indirectly on-board the vessel as a result of beingprovided at least in part on a structure which rotates or oscillateswith the vessel. In the former case for instance, the monitoring meansmay be mounted on a wall of the vessel while in the latter case themonitoring means may be carried at least in part by a frame whichsupports the vessel and through the agency of which the vessel isrotated or oscillated. References herein to the monitoring means beingdirectly or indirectly on-board the vessel are to construed as referringthe foregoing possibilities.

The profiles derived from scanning (hereinafter the “scanned profiles”)may be monitored for convergence towards a static condition. This mayfor example involve comparison with a predetermined target spectroscopicprofile. In this context, it is to be understood that the initialspectra of the components before mixing will correspond generally to thespectrum of each of the components. As the mixing process proceeds, thespectra of the mixture will undergo change and begin to converge towardsthe spectra of the homogeneous mixture. Thus, the mixing process can becontrolled with reference to the spectroscopic profile obtained by themonitoring means and, in particular, may be terminated when the scannedprofiles meet a predetermined criterion, e.g. when the scanned profilesattain or converge towards a substantially static condition. This mayfor example be satisfied when the scanned profile substantially matchesthe target profile or when two or more scanned profiles (or partsthereof) of the mixture are substantially the same or differ from oneanother by no more than a predefined extent.

Where used, the target profile may be representative of a selectedcondition of the mixture; for instance, it may be representative of thehomogeneous end-point for a mixture of the components undergoingblending or an intermediate state lying between the homogeneous endpoint and the unmixed state.

Often the components undergoing mixing will have different chemicalcompositions. However, the invention also encompasses the mixing ofcomponents having the same or substantially the same chemicalcomposition. For example, the apparatus of the invention may be used formixing components which have the same or substantially the same chemicalcomposition but have differing physical characteristics, such asmoisture content, particle distribution etc. Thus, one application ofthe invention lies in the combining of two fractions of the samematerial, one fraction comprising fines and the other comprising coarserparticles, the mixing process being carried out to produce a mixture inwhich the fines are dispersed into the coarser particles, e.g. to securea substantially uniform distribution of fines in the mixture.

Control means responsive to the monitoring means may be provided forcontrolling the mixing process.

Thus, the drive means may be controlled by the control means independence upon the result of the comparison so that the mixing processcan be terminated when the profiles derived from scanning converge on orsubstantially match the predetermined profile or converge towards astatic condition where the changes in scanned profiles (or parts thereofare no greater than a predefined extent.

The monitoring means may include or be associated with comparison meansfor comparing spectroscopic profiles corresponding to thescanning-derived data with the target profile or previously derivedscanned profiles obtained during a given mixing cycle. Thus, themonitoring means may embody the comparison means so that the comparisonof scanned profiles with target profile or previously derived scannedprofiles is effected during rotation or oscillation of the monitoringmeans with the vessel.

When the scanned profiles have converged to a predetermined extenttowards a static condition (e.g. when a desired level of matchingbetween the scanned profile and a target profile is obtained), themonitoring means may be arranged to supply an output signal to signalutilising means for controlling the mixing process. For instance, thesignal utilising means may be operable in response to receiving theoutput signal to terminate the mixing process by suitable control of thedrive means, e.g. by disabling the drive means and terminating rotary orangular movement of the vessel.

In an alternative embodiment, the comparison means may be separate fromthe monitoring means and the vessel. In this case, data transferringmeans will be provided for transferring scanning-derived data from themonitoring means to the comparison means. The data transferring meansmay for example comprise a signal transmitter directly or indirectlyon-board the vessel and a receiver associated with the comparison meanswhereby the data is transmitted radiatively from the monitoring means tothe comparison means.

Matching of the newly derived scanned and target or previously obtainedscanning profiles (at least to the desired extent) conveniently leads toautomatic termination of the mixing process. However, we do not excludethe possibility that such matching, whether carried out directly orindirectly on-board the vessel or elsewhere, may instead give rise to anoutput signal, e.g. visual or audible, suitable for attracting anoperator's attention to the fact that mixing to an acceptable level,e.g. an acceptable level of homogeneity, has been secured and that themixing process can be terminated and the mixture transferred to asubsequent processing stage.

The monitoring means is preferably self-powered and to this endconveniently includes a power source which may be in the form of one ormore batteries, preferably rechargeable batteries.

Where comparison of the newly derived profiles and target or previouslyderived profiles is carried out directly or indirectly on-board thevessel, the monitoring means may include data storage means for storingthe scanning-derived data, optinally together with at least onepredetermined target profile where applicable. The scanning-derived datacollected during the course of a mixing process may then, during or oncompletion of a mixing cycle, be transferred to separate dataacquisition means to allow a record to be maintained for a series ofmixing cycles.

The monitoring means conveniently includes a signal transmitter fortransmitting signals radiatively to a receiver located in the vicinityof or remotely from the vessel thereby eliminating hard-wiredconnections (such as electrical conductors, optical fibres and the like)between the monitoring means and signal utilising means and/or a dataacquisition means linked to the receiver. For instance, the transmittedsignal may be in the form of a radiation signal such as a radiofrequency signal.

In a preferred embodiment, the monitoring means comprises aself-contained unit capable of being battery-powered and is providedwith means for detachably docking the unit with the vessel, preferablynon-invasively, or with structure which rotates or oscillates with thevessel so that the scanning means is in registry with a window throughwhich spectroscopic data is obtained.

Where the monitoring means is battery powered, the battery supply mayform part of the self-contained unit or it may comprise a separate unitwhich may be provided directly or indirectly on-board the vessel. Inthis event, because the battery supply unit and the monitoring meansboth rotate or oscillate with the vessel, there may be a hard-wiredconnection between the two.

The self-contained unit will typically comprise at least the scanningmeans, a radiative signal transmitter, and optionally a compartment orcompartments containing or for reception of a battery or batteries forpowering the unit. In addition, the self-contained unit may include datastorage means and said comparison means; for instance, the data storagemeans and the comparison means may both be embodied in a microprocessoror computer forming part of the unit.

The self-contained unit is conveniently docked with the vessel inregistry with the window by means of releasable, preferablyquick-release, devices, e.g. in the form of one or more latching devicesco-operating with a keeper or keepers. The releasable devices arepreferably arranged to clamp the unit securely to the vessel. One formof suitable device comprises a sprung draw latch commercially fromSouthco Europe Limited of Cheltenham, England.

Instead of being mounted for rotation or oscillation with the vessel,the monitoring means may be located at a fixed position, the arrangementbeing such that the monitoring means “views” the contents of the vesselat least during part of its cycle of rotation or oscillation. Thus, forexample, the vessel may be provided with a window through whichmonitoring means “views” the contents of the vessel as the windowtraverses the line of sight of the monitoring means. The window may bestrategically located at that part of the vessel which makes the closestapproach to the monitoring means during each cycle of rotation oroscillation of the vessel and the window may be of elongatedconfiguration in the direction of travel past the monitoring means so asto afford an extended interval of “viewing”.

The monitoring means may be operable at only predetermined points duringeach cycle of rotation or oscillation of the vessel.

Means may be provided to sense the angular position of the vessel withrespect to a datum position and, if desired, control operation of themonitoring means so that data relating to the mixture is only collectedat said predetermined points. The monitoring means may be disabled atother times. Such predetermined points may for instance correspond topoints during said cycle when the mixture can be expected to be incontact with the wall of the vessel at the location “viewed” by themonitoring means.

A preferred alternative however is to arrange the monitoring means tocollect data substantially continuously throughout the cycle of rotationor oscillation (e.g. at the rate of one scan per second) and, from thedata collected, discriminate between data corresponding to the points inthe cycle when the mixture makes suitable contact with the window, i.e.data representative and data unrepresentative of the state of mixing. Inthis case, it may not be necessary to provide means for determining theangular position of the vessel.

Particularly but not necessarily exclusively where the monitoring meansis fixed relative to the moving vessel, the vessel may, with respect tothe radiation used for monitoring, be substantially transparent over anextended or substantially the entire area thereof.

The walls of the vessel may be fabricated at least in part, e.g. atleast a major part and possibly substantially entirely, from a plasticsmaterial. The plastics material may be one which is transparent withrespect to the radiation used (e.g. near infra red radiation).

While the vessel will normally comprise a rigid structure, usually ofmetal such as stainless steel, we do not exclude the possibility of thevessel being constituted by a flexible bag, e.g. of a plastics material.The bag and monitoring means may be adapted to enable the monitoringmeans to be coupled to the bag or the monitoring means may be mountedseparately from the bag either in fixed relation to the bag or on astructure that rotates or oscillates with the bag, as described above.

Various other aspects of the invention are indicated below which otheraspects may, where the context admits, be combined with each otherand/or with said one aspect and/or any of the other features definedabove.

According to a second aspect of the present invention there is providedapparatus for mixing a number of components (for example to produce ahomogeneous mixture), comprising a vessel for receiving the components,drive means for rotating or oscillating the vessel about an axis toeffect mixing of the components within the vessel, and at least onespectroscopic monitoring means provided directly or indirectly on-boardthe vessel for repeatedly scanning the mixture to obtain data for use inmonitoring changes in the spectroscopic profile of the mixture as mixingproceeds, the monitoring means being in the form of a self-containedunit mounted releasably on the vessel.

According to a third aspect of the present invention there is providedapparatus for mixing a number of components (for example to produce ahomogeneous mixture), comprising a vessel for receiving the components,drive means for rotating or oscillating the vessel about an axis toeffect mixing of the components within the vessel, and at least onespectroscopic monitoring means provided directly or indirectly on-boardthe vessel for repeatedly scanning the mixture to obtain data for use inmonitoring changes in the spectroscopic profile of the mixture as mixingproceeds, the monitoring means including means for radiativelytransmitting to an off-board receiver an output for use in controllingthe mixing process.

According to another aspect of the invention there is provided apparatusfor mixing a number of components (for example, to produce a homogeneousmixture), comprising a mixing zone for receiving the components, meansfor mixing of the components within the mixing zone, and at least onespectroscopic monitoring means for repeatedly scanning the mixturewithin and/or downstream of the mixing zone to obtain and record datafor use in monitoring changes in the spectroscopic profile of themixture as mixing proceeds, means responsive to the monitoring means formodifying, e.g. terminating, the mixing process when the spectroscopicdata obtained signifies attainment of a desired level of mixing and dataacquisition means for collecting recorded data from the monitoringmeans, the data acquisition means having a docking station with whichthe monitoring means can be docked on completion of the mixing processto allow transfer of recorded data from the monitoring means to the dataacquisition means.

To facilitate docking the monitoring means is preferably in the form ofa portable unit, e.g. hand portable, adapted for detachable mounting ona wall of the mixing zone so that, on completion of the mixing cycle,the monitoring means can be dismounted and transported, e.g. manually,to the docking station. For the purposes of portability, the unitincorporating the monitoring means will usually conform with HSE ManualHandling Operations Regulations 1992 and will typically be no more than25 kg in weight, preferably less.

A guide rail or rails may be provided on the vessel for locating theunit in a desired position, e.g. with the monitoring means properlyregistered with the window, so that the unit may initially be engagedwith the guide rail(s) and then adjusted by sliding the same along therail(s) to the desired position before securing it in that position withthe aid of releasable fastening devices.

The docking arrangement may include one or more hook formations on theunit and a support or supports on the vessel so that the unit can beoffered up to the vessel by hooking the hook formation(s) to thesupport(s) which may comprise a rail to permit sliding adjustment of theunit after engaging the hooks with the rail. In this way, the unit maybe temporarily suspended from the support(s) to free the hands of theoperator and thereby allow him to operate a fastening device or devicesto secure the unit in place so that the unit is held in place by thehook formation(s)/support and the fastening device(s).

The monitoring means may be provided with one or more handles to aidmanipulation during detachment from the wall of the mixing zone, dockingwith the data acquisition means and/or transport between the mixing zoneand the data acquisition means.

The rotatable or oscillatable mixing vessel may comprise a so-calledV-blender of the type described in EP-A-0631810, the relevant disclosureof which is incorporated herein by this reference.

Alternatively, and more preferably, the rotatable or oscillatable mixingvessel may comprise a so-called Intermediate Bulk Container (IBC)designed for use in conjunction with an installation comprising a driveunit and a mounting frame for receiving and supporting the IBC, themounting frame being coupled with the drive unit for rotation about anaxis to effect tumbling of the components within the IBC as the latterrotates with the mounting frame.

In accordance with another aspect of the present invention there isprovided an IBC provided with a window allowing for the scanning of thecontents thereof by spectroscopic monitoring means, preferably nearinfrared spectroscopic monitoring means.

In accordance with a further aspect of the invention there is providedan IBC provided with docking means for the releasable mounting of aspectroscopic monitoring means for the scanning of the contents of theIBC.

Also in accordance with the invention there is provided an IBC providedwith a spectroscopic monitoring means for the scanning of the contentsof the IBC, the monitoring means preferably being non-invasively mountedon the IBC in registry with a window through which the scanningradiation is transmitted.

Usually the IBC is in the form of a hopper, typically of generallyrectangular cross-section, with an inlet for components to be mixed at alarge cross-section upper part of the IBC and an outlet for discharge ofthe mixture at a somewhat smaller cross-sectional lower part.

The IBC may be provided with means for coupling the same to a drive unitfor rotating or oscillating the IBC, usually about an axis which extendsobliquely with respect to the IBC, e.g. such that the axis of rotationor oscillation does not intersect the axis about which the IBC isgenerally symmetrical.

The IBC is conveniently transportable; for instance, it may be providedwith ground-engaging wheels or may be adapted for mounting on a wheeledvehicle such as a trolley.

The coupling between the IBC and the drive unit may be through theagency of a mounting frame associated with the IBC or the drive unit.

Where the mounting frame is associated with the drive unit, the framemay comprise upper and lower sections which are relatively movabletowards and away from one another between a loading position in whichthe IBC may be introduced into the mounting frame and a clampingposition in which the IBC is raised out of contact with the ground andsecurely clamped for rotation with the frame.

The frame may be supported from a shaft of the drive unit for rotationabout an axis which is obliquely orientated with respect to a centralaxis of the frame whereby the IBC and its contents are rotated an axiswhich is oblique with respect to the axes about which the IBC isgenerally symmetrical. The axis of rotation for instance may besubstantially horizontal and the mounting frame may have a generallyhorizontal axis about which it is substantially symmetrical and which isinclined in a horizontal plane with respect to the rotational axis ofthe drive means, e.g. at an angle which may range from about 10° toabout 40°, with 17° and 30° being typical angles of obliqueness.

While the monitoring means is preferably provided directly on the IBC,we do not exclude the possibility that the monitoring means may beprovided on the mounting frame and arranged to effect monitoring thecontents of the IBC, e.g. through a strategically located windowprovided in a wall of the IBC.

According to a further aspect of the present invention there is providedapparatus for mixing a number of components (for example to produce ahomogeneous mixture), comprising a housing having an inlet and an outletfor receiving the components and means for effecting feed of thecomponents from the inlet to the outlet while effecting mixing thereof,means for feeding the components to the inlet while mixing is takingplace and means for collecting the mixture from the outlet while mixingis taking place, the housing being provided with at least one nearinfrared spectroscopic monitoring means for repeatedly scanning themixture within the mixing zone and/or downstream thereof to obtain datafor use in monitoring changes in the spectroscopic profile of themixture.

The monitoring means may be arranged to scan the mixture in the mixingzone and/or a point downstream of the outlet, e.g. in a conduitconnected to receive the mixed components from the mixing zone.

In this last-mentioned aspect of the invention, the monitoring means maybe deployed to scan the mixture at a location along the path of travelthrough the housing and/or downstream of the outlet where the mixturewould normally be expected to be in the desired state, e.g.substantially homogeneous, and comparison means may be provided forcomparing the scanned spectroscopic profile of the mixture withpreviously obtained scanned profiles or with a predetermined targetprofile representing the desired state, e.g. homogeneous end point, forthe mixture. In this way, if the comparison indicates that the mixturehas not attained the desired state, the mixing process can be modifiedor terminated to allow remedial action to be taken.

In one embodiment of the invention according to this aspect of theinvention, the mixing zone is within a stationary housing and mixing iseffected by means of a rotatable or angulary oscillatable mixing devicewhich also serves to feed the mixture of components towards the outlet.

The monitoring means employed in the present invention is preferably anear infra red spectroscopic unit having a solid state tunable filter,such as an acoustic-optic tunable filter.

The invention also resides in a method of mixing including, inter alia,the following aspects considered individually or, where the contextadmits, in combination with each other and/or in combination withaspects and features of the invention referred to above:

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing thecomponents into a mixing vessel, rotating or oscillating the mixingvessel to effect mixing of the components and non-invasively monitoringmixing by collecting spectroscopic data from the mixture during rotationor oscillation of the vessel.

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing thecomponents into a mixing vessel, rotating or oscillating the mixingvessel to effect mixing of the components, monitoring mixing bycollecting and optionally analysing spectroscopic data from the mixtureby means of spectroscopic monitoring means which rotates or oscillateswith the vessel.

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing thecomponents into a mixing vessel which has an axis about which it issubstantially symmetrical, rotating or oscillating the mixing vesselabout an axis which extends obliquely relative to said vessel axis toeffect mixing of the components and monitoring mixing by collectingspectroscopic data from the mixture during rotation or oscillation ofthe vessel.

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing thecomponents into an IBC, rotating or oscillating the IBC to effect mixingof the components and monitoring mixing by collecting spectroscopic datafrom the mixture.

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing atleast one of the components into a mixing zone, in a first phase ofoperation effecting mixing while monitoring the condition of said atleast one component by collecting spectroscopic data representative ofsuch condition, on detection that said at least one component hasattained a desired condition adding at least one additional component tothe mixing zone and, in a second phase of operation, effecting mixingwhile monitoring the condition of the mixture as supplemented with saidadditional component by collecting spectroscopic data representative ofsuch condition to determine the attainment of a desired condition ofsaid supplemented mixture.

The above aspect of the invention may be carried out in a rotating oroscillating vessel or it may be carried in a non-rotating vessel orconduit provided with mixing means such as a bladed rotor or an orbitingscrew mixer. In the case of a non-rotating vessel or conduit, thematerial may be fed continuously through the mixing zone and theadditional component or components may be introduced at one or morelocations downstream of the point of introduction of said at least onecomponent.

A method of mixing a number of components (for example to produce asubstantially homogeneous mixture thereof) comprising introducing atleast one of the components into a mixing vessel, in a first phase ofoperation rotating or oscillating the vessel while monitoring thecondition of said at least one component by collecting spectroscopicdata representative of such condition, on detection that said at leastone component has attained a desired condition adding at least oneadditional component to the mixing vessel and, in a second phase ofoperation, rotating or oscillating the vessel while monitoring thecondition of the mixture as supplemented with said additional componentby collecting spectroscopic data representative of such condition todetermine the attainment of a desired condition of said supplementedmixture.

A typical application lies in mixing pharmaceutical components where oneof the components comprises a lubricant such as magnesium stearate. Carehas to be exercised in ensuring that the lubricant does not fully coatthe particles of said pharmaceutical components (sometimes referred toas overblending) otherwise subsequent tabletting of the mixture is notpossible. Thus, in the last two mentioned aspects of the invention, thefirst phase may comprise partial blending of the pharmaceuticalcomponents in the absence of the lubricant component, while the secondphase may comprise addition of the lubricant component and completion ofblending with the excipients and active to a desired level ofhomogeneity (but without overblending).

In the foregoing, two phases of mixing while collecting spectroscopicdata are mentioned but it will be appreciated that there may be morethan two such phases. For instance, there may be a further phase orphases in which a further component or components are added and mixingcontinued while collecting spectroscopic data allowing the attainment ofthe desired condition to be determined.

The condition monitored in the first phase may be of the same nature asthat for monitored during the second stage. For example, in both phases,the condition monitored may be related to the level of homogeneityattained, i.e. substantially fully homogeneous or an acceptable levellying between for instance the fully inhomogeneous and the fullyhomogeneous states.

However, the conditions monitored need not be of the same nature. Forinstance, in the first phase, the components introduced may be in theform of fines and coarser particles and the first phase may comprisemonitoring the extent of distribution of fines within the mass of coarseparticles while the second phase, after introduction of the additionalcomponent(s), may involve monitoring for the attainment of thehomogeneous endpoint or some other acceptable level of blending.

It will be appreciated that, where the context admits, the variousmethod aspects of the invention may be carried out using the variousaspects and features of the apparatus and/or IBC as described above. Inparticular, the method of the invention in its various aspects ispreferably carried out using an acoustic optic tunable filter(preferably one based on a tellurium dioxide crystal) to produce, from abroad band radiation source (preferably a near infra red source),radiation at a wider range of different wavelengths or within differentbands.

The invention will now be described by way of example only withreference to the accompanying drawings, in which:

FIG. 1 is a diagrammatic view of a so-called V-blender and an associatedblending process arrangement;

FIG. 2 is a block diagram of a spectroscopic monitoring unit formingpart of the apparatus of FIG. 1;

FIG. 2A is a diagrammatic view showing docking of the monitoring unitwith a data acquisition and analysis unit;

FIG. 3 is a diagrammatic view of a continuously operable blenderprovided with a spectroscopic monitoring unit;

FIG. 4 is a diagrammatic view of a IBC;

FIG. 5 is a diagrammatic side view illustrating the loading position ofa frame for mounting the IBC;

FIG. 6 is a similar view to that of FIG. 5 but showing the IBC is theraised, secured position in preparation for rotation and mixing of theIBC contents;

FIG. 7 is a diagrammatic plan view showing the orientation of themounting frame and the IBC;

FIG. 8 is a diagrammatic view of a probe arrangement for transmissionscanning of the mixing zone;

FIG. 9 is a front elevational view of an integrated framework and IBCarrangement with part of one of the uprights broken away to afford aview of the viewing window provided on the IBC;

FIG. 10 is an enlarged view of that part of the IBC provided with meansfor docking of the monitoring means;

FIG. 10A is a diagrammatic plan view showing the axis about which theIBC is rotated; and

FIGS. 11 and 12 are graphs in 3 dimensions and 2 dimensions respectivelyillustrating convergence of spectroscopic profiles during the course ofa mixing cycle.

Referring to FIG. 1, blending of powders such as pharmaceutical activesand excipients is carried out in a V-blender. The design and operationof such blenders is well-known to those skilled in the art (for example,see EP-A-0631810). Briefly the V-blender comprises a vessel 10 which isgenerally V-shaped with two legs 12 and access openings 14 and 16respectively located at the intersection between the legs and at thefree ends of the legs 12. The openings 14, 16 allow the introduction ofthe components to be blended and their subsequent removal, each openingbeing provided with a closure member which is secured in place bysuitable releasable fasteners (not shown). The vessel is mounted forrotation about an axis 18 which passes through the interior of thevessel. Thus, as shown, the vessel is provided with co-axial shafts 20located on opposite sides of the vessel. The shafts are supported insuitable journals 22 and are coupled to the vessel in such a way thatthe shaft couplings are non-invasive, i.e. they do not project into theinterior of the vessel and thereby potentially interfere with theblending process. One of the shafts is coupled to drive means 24 whichtypically comprises an electric motor and drive transmission means.

At a suitably strategic position, the vessel is provided with a window26, the interior surface of which is substantially flush with theinterior surface of the vessel walls so as to be non-invasive. At thislocation, a spectroscopic monitoring unit M is mounted on-board thevessel. The window location is selected so that scanning of the mixtureof components at that location will provide representative spectroscopicprofiles of the overall state of blending attained during the blendingprocess. The window may of any suitable material compatible withtransmitting the radiation without distortion; for example, in the caseof near infrared radiation, the window may be of sapphire.

The monitoring unit in this embodiment houses a mixture scanningtransducer 28 which under the control of control circuitry 30 generatesradiation, e.g. near infrared radiation, for transmission into thevessel via the window 26 and receives radiation reflected back by themixture of components immediately adjacent the interior surface of thewindow. Data corresponding to the reflected signal is stored in datastorage means, e.g. a solid state data storage device (such as a RAMchip), forming part of computing means 34 which is programmed to analysethe data to derive, for each scan, a spectroscopic profile and may forexample compare the scanned profile with a preloaded target profilerepresenting the homogeneous end-point for the mixture of componentsundergoing blending. Scanning of the mixture is carried out repeatedlythroughout the blending operation and the data collected during eachscan is retained in the storage device. For instance, scanning may becarried out so as to obtain at least one spectroscopic profile perrevolution of the vessel; typically in practice, hundreds or even inexcess of one thousand such spectroscopic profiles may be obtainedduring each revolution. The mixing vessel typically rotates at a rate ofabout 7 to 8 rpm.

The monitoring unit M may continuously collect data through eachrevolution of the vessel. Some of the data collected of course may notbe relevant since there will be periods of time during each revolutionwhen the material is not present, or at least not present in a suitablypacked form, immediately adjacent the viewing window. Nevertheless, thisdata may be collected and stored but can be identified, by virtue of thecorresponding spectroscopic profile, as being of no relevance to thestate of blending actually prevailing. At other times during therotational cycle, the material will be resident at the window in apacked condition suitable for determination of the state of blending.The extent of packing may vary to some extent but sensitivity of themonitoring means to this variation may be controlled by appropriateselection of the wavelengths used in scanning.

The computing means 34 may store a number of target profiles eachcorresponding to a different set of components, or proportions, to beblended and is provided with user-input means (e.g. a dial, numerickeyboard or the like—not shown) by means of which the target profileappropriate for a given blending operation can be selected for thepurpose of comparison with the scanned profiles. Instead of assessingthe degree of mixing by reference to a predetermined target profile orprofiles, the computing means may monitor changes in the data derived byscanning in order to identify convergence of the data towards asubstantially static condition which may be equated with a desireddegree of mixing. Thus, for example, the computing means may beprogrammed to average the data derived from a predetermined set of scansand determine the extent to which the averages are moving from one setof scans to the next so that once the average values converge and nolonger fluctuate by more than a predetermined amount, this may be takento represent a static condition corresponding to a desired state ofmixing.

In practice, for the reasons mentioned above, the spectroscopic profilesobtained from each scan can vary substantially depending on theorientation of the vessel, i.e. some scans may correspond to a full viewof the powder components while other scans may correspond to viewingfree space. The computing means is therefore programmed to differentiatebetween “good” scans representative of the degree of mixing prevailingand “free space” scans. This may for instance involve comparingreflectance values at one or more wavelengths with a predeterminedthreshold value or values and rejecting those spectra with reflectancevalues less than the threshold value(s) and/or supplying the computingmeans with data signals indicating the rotational orientation of thevessel at one or more points in its cycle of rotation (or oscillation).

The spectroscopic technique employed may be near infrared spectroscopypreferably operating over the frequency range from 900 to 2500 nm.However, the invention is not limited to use of the near infrared regionand other forms of spectroscopic device operating in the region ofelectromagnetic radiation wavelengths may be used such as anultraviolet-visible spectrophotometer, a mid-range infraredspectrophotometer, an infrared spectrophotometer or a Ramanspectrophotometer.

The unit M also includes a signal transmitter 36 for producing an outputsignal when the result of the profile comparison made by the computingmeans 34 establishes that the scanned profile matches the targetprofile, or is at least an acceptable match within predefined tolerancesprogrammed into the computer means. The output signal so emitted may bea visual and/or audible signal for alerting an operator to the fact thatthe desired degree of mixing, e.g. the homogeneous end point, has beenattained so that the operator can then terminate the blending cycle byswitching off the drive motor. The signal transmitter 36 may in thisinstance be provided with a light source for producing a visual output,e.g. a flashing output, and/or a sound source such as a speaker foremitting an audible signal.

Alternatively the output signal may be used to terminate, or initiatetermination of, the blending cycle automatically. In this case, thesignal transmitter 36 may emit electromagnetic signals (e.g. radiofrequency signals) for reception by a receiver forming part of controlcircuitry 38 associated with the drive means 24 so that, on receipt ofthe “matched” signal from the transmitter 36, the blending vessel can bebrought to rest by shutting down the drive means.

The signals produced by the signal transmitter are preferably capable ofbeing discriminated from the signals emitted by similar signaltransmitters associated with other blenders/monitoring units M in thevicinity. Where the signals are radiatively transmitted, suchdiscrimination may be by way of the frequency of transmission or thesignals from different transmitters may be encoded differently from oneanother. Where the signals are in visual and/or audible form,discrimination may be achieved by using different colours, flashingregimes, sound frequencies, sound spectra etc or even by electronicallygenerated spoken output stating that a given blending vessel hascompleted its cycle (or wording to that effect).

The unit M is self-contained in that it collects and storesspectroscopic data from the vessel, makes a comparison between thescanned spectral profiles and the appropriate target profile. It is alsoself-powered, the power supply for the various components of the unitbeing in the form of one or more batteries (e.g. rechargeable batteries)accommodated by the unit M. Further, it may be sufficiently light andcompact to be portable without the aid of mechanical handling equipmentand for this purpose may be fitted with one or more handles H tofacilitate carrying of the unit and mounting/dismounting operations ofthe unit relative to the blending vessel. The unit M may for instancecomprise a common frame or base on which the various components aremounted.

The unit M is designed for rapid mounting and dismounting and, for thispurpose, is provided with one or more releasable devices, by means ofwhich the unit M can be secured to the vessel in defined orientationrelative to the window 26, e.g. with the frame or base clamped to thevessel at a predefined docking location on the vessel. For instance, theunit may be provided with one or more latching members 29, e.g. Southcosprung draw latches, for co-operation with one or more correspondingkeepers provided on the vessel (or vice versa), e.g. so arranged thatthe unit M has to be offered up to the vessel in a certain orientationin order to effect correct docking with the latch/latches andkeeper/keepers correctly aligned for securing action. It will be notedthat the unit M is mounted off-axis relative to the axis of rotation ofthe blender and that the spectroscopic scanning is effectednon-invasively.

All of the data collected by the data storage device of the computingmeans 34 during a blending cycle is potentially of use for example inanalysing the performance of the blender and the unit M. On completionof the blending cycle, the collected data is transferred to anelectronic data acquisition and analysis unit (DAAU, not shown). TheDAAU may be equipped with a defined docking location of similar designto that on the vessel so that fastening devices provided on the unit Mmay be used to secure the unit M to the DAAU during data transfer. TheDAAU may include means for relating the transferred data with forexample the particular blender, the monitoring unit M used and/or theblending cycle performed; for instance, the DAAU may include inputmeans, e.g a keyboard or the like, for such identification data. Oncedata transfer to the DAAU has been effected, the scanning-derived datastored in the unit M from the relevant blending cycle may be deleted oroverwritten in a subsequent blending cycle.

The unit M also includes a compartment for a power supply 40, e.g. inthe form of a rechargeable battery or batteries. The power supply 40 maybe maintained fully effective by removing the rechargeable battery orbatteries during the downtime between successive blending operations andsubstituting a fully charged battery or batteries, the replacedbatteries then being put on recharge in readiness for insertion into thesame unit or another monitoring unit once fully recharged.

In the embodiment described with reference to FIGS. 1 and 2 (and alsothose described hereinafter) analaysis of the scanned data, e.g.comparison of the scanned profiles with a target profile, is carried outon-board and the signal to terminate the blending operation is emittedby the on-board transmitter. Various modifications are possible,including for example “off-board” data storage and/or data analysis,e.g. comparison of scanned and target profiles, during the blendingcycle. For instance, the data obtained by repeated scanning may betransferred from the unit M to a separate “off-board” computing meanshaving a data storage facility and programmed to analyse the data inorder to determine the attainment of a desired degree of blending. Datatransfer from the unit M to the computing means may in this case beeffected by radiative transmission from the transmitter 36, e.g. by wayof radio frequency signal coded with the data undergoing transfer, to areceiver associated with the computing means. In such embodiments,control of the drive means for the blending vessel may be effected bysignals derived from the computing means, e.g. representing “matching”of the scanned and target profiles, and such signals may be transferredto the control circuitry 38 associated with the drive means eitherthrough radiative transmission using a transmitter-receiver pair or by ahard-wired connection.

Also while FIGS. 1 and 2 illustrate the use of a single monitoring unitM, it will be appreciated that each blender may be equipped with morethan one on-board monitoring unit and window combination located atdifferent strategic locations on the vessel. Moreover, instead of themonitoring unit or units M being battery powered, we do not exclude thepossibility of powering the same from a separate off-board electricalpower source (e.g. the mains supply) via cabling which may be coupled toan on-board monitoring unit via slip rings or other couplings allowingelectrical connections to be made to the monitoring unit when mounted onthe rotating or oscillating vessel.

Referring now to FIG. 3, this illustrates an embodiment of the inventionin which blending or mixing of the components is effected on acontinuous rather than a batch basis within a passageway defined by ahousing 50 having an inlet 52 for introduction of the components to beblended and an outlet 54 of removal of the blended mixture. The blendingprocess is continuous in this embodiment in the sense that componentsare being fed to the blender and homogeneously blended mixture removedtherefrom while blending is taking place within the housing 50. Mixingis effected by a shaft mounted agitator 55 (e.g. an auger-type device)which can rotate or oscillate angularly about the shaft axis to tumbleand mix the components while advancing them from the inlet to theoutlet. A window 56 (e.g. a sapphire window) is strategically located onthe housing at a point along the path of travel of the mixture where thecomponents have undergone sufficient mixing that the homogeneous endpoint will normally have been attained or is sufficiently close thathomogeneity will inevitably occur as the mixture travels through theremainder of the housing.

The housing 50 is provided with a monitoring unit M which may besubstantially as described with reference to FIGS. 1 and 2 and may becoupled to the housing 50 at a docking location including the window 56so that spectroscopic data can be collected for analysis, for instanceusing the techniques referred to above in relation to the embodiment ofFIGS. 1 and 2. In this case the analysis, e.g. comparison between thescanned and target profiles, is used as a check to ensure that thedesired level of homogeneity is being secured during the continuousblending of the components. If the comparison reveals that the scannedprofiles are not sufficiently matched with the target profile, themonitoring unit M is operable to produce a signal either to alert anoperator to the fact that inadequate blending is occurring or toterminate the blending process, i.e. as described above in relation toFIGS. 1 and 2. Again the monitoring unit M will be portable andattachable to the housing 50 by a quick release device or devices. Also,it may be designed for docking with a data acquisition and analysis unitas described previously.

In the embodiment of FIG. 3, the monitoring unit M is not mounted on arotating part of the blending equipment. Consequently, transmission ofsignals from the unit M may be more readily be effected by way ofhard-wired connections, although we do not exclude the possibility ofradiative transmission. Also while this embodiment illustrates a housing50 which comprises a conduit in which the mixer rotates about a fixedaxis generally concentric with the axis of the housing, in amodification, the housing may be generally hopper-shaped and the mixermay be an orbiting screw mixer.

The spectroscopic monitoring unit M as used in the embodiments describedabove and hereinafter may include a solid state tellurium dioxidenon-collinear acoustic-optic tunable filter of the type disclosed in thearticle “Acoustic-Optic Tunable Filters Spectrally Modulate Light” by DrXiaolu Wang and published in the August 1994 edition of Laser FocusWorld (the entire disclosure of which is incorporated herein by thisreference). As described in that article, the filter may be associatedwith a tungsten lamp to provide a fast tuning near infrared source forspectroscopic applications. The detector used may be In—Ga—As detector.A suitable form of spectroscopic monitoring unit for use in the presentinvention is the Luminar 3030-701-INT AOTF-NIR Free Space Spectrometer,wavelength range 1100 to 2300 nm (and also the corresponding 2030 model,wavelength range 900 to 2300 nm) commercially available from BrimroseCorporation of Baltimore, Md. 21236, USA. Another device that may beemployed in embodiments of the present invention is the NIR OpticalSpectrograph Card (NIROSC), including an In—Ga—As diode array, availablefrom Control Development Corporation of Indiana, USA.

Various other forms of spectroscopic unit may be used. The radiationsource may be a broad spectrum visible to infra-red source, such as atungsten-halogen lamp, which emits radiation in the near infra-redinterval of from 400 to 2500 nm. While it is preferred that the filterarrangement is constituted by an AOTF as mentioned above, the filterarrangement may comprise a plurality of filters each allowing thepassage of radiation of a respective single frequency or frequency band.In other embodiments the radiation source could be any of a source ofvisible light, such as an arc lamp, a source of x-rays, a laser, such asa diode laser, or a light-emitting diode (LED) and the filterarrangement could be replaced by a diffraction grating, a monochromatoror a spectrometer of Fourier transform kind.

The detector may be an integrating detector, such as an Si, PbS orIn—Ga—As integrating detector, a diode array detector, such as an Si orIn—Ga—As diode array detector, or a one or two-dimensional arraydetector, such as a CMOS chip, a CCD chip or a focal plane array. Inuse, the detector will produce signals depending upon the composition ofthe mixed material and the frequency of the provided radiation.

Referring now to FIGS. 4 and 5, a particularly convenient implementationof the invention is possible using a so-called IBC and driveinstallation for mounting and for rotating the IBC. Such installationsare commercially available from Matcon U.K. of Gloucestershire, UK. TheIBC comprises a hopper-shaped vessel 100 having an inlet port 102 at itsupper larger cross-sectional part and an outlet 104 at its lowercross-sectional part. Components to be mixed are introduced into the IBCthrough the inlet port and the mixture is discharged through the outletport 104 which may be equipped with means (not shown) for facilitatingsuch discharge. Such means may for instance comprise Matcon cone valvetechnology. The inlet and outlet ports are provided with closure means(not shown). The IBC is generally symmetrical about its vertical axiswith a larger cross-section upper part and a lower part having aprogressively reducing cross-section towards the outlet 104, i.e. as aresult of its hopper configuration. The IBC is typically of rectangularcross-section in the horizontal plane

The IBC is adapted to be mounted on a drive unit 106 having a driveshaft 108 to which an IBC mounting frame 109 is coupled. The frame 109comprises upper and lower frame parts 110, 112 which are relativelymovable towards and away from each other (e.g. the lower frame 112 maybe movable and the upper frame 110 may be fixed) between an IBC loadingposition as illustrated in FIG. 5 and an IBC supporting position asillustrated in FIG. 6 in which the IBC is raised out clear of the groundand is securely clamped for rotation with the frame 109. As shown in theplan view of FIG. 7, the frame 109 is mounted on the drive shaft 108 insuch a way the generally vertical plane of symmetry of the frame isobliquely inclined relative to the rotation axis 114 of the shaft 108.Likewise when the IBC is mounted in the frame as shown in FIG. 6, thehorizontal axis 116 about which the IBC is generally symmetrical extendsobliquely relative to the rotation axis 114. In operation, the obliquelymounted IBC is rotated about the axis 114 to effect mixing of itscontents.

The IBC is equipped with a monitoring unit M which is coupled to astrategically located docking station on the IBC, e.g. on one of theinclined side walls thereof. The unit M is generally of the same designas and may have all of the characteristics as described in relation tothe unit M of FIGS. 1 and 2 and, when docked, will be in registry with awindow (not shown) in the side wall so that scanning of the contents ofthe IBC can be effected during the mixing process. The monitoring unit Mmay for example comprise a Brimrose battery-powered spectroscope AOTFunit as referred to above. As in the embodiment of FIG. 2, themonitoring unit M may be designed to control the mixing cycle, e.g. byproduction of a signal which is transmitted to an off-board receiver andassociated signal utilising means which controls the drive unit 106.Thus, for instance, when the spectroscopic data collected by themonitoring unit M indicates that the mixture has progressed to a desiredcondition, e.g. the homogeneous endpoint for the mixture, the monitoringunit may emit a signal which triggers operation of the drive unit 106 toterminate rotation of the frame 109 and position the IBC in theconfiguration shown in FIG. 6 to allow the contents of the IBC to bedischarged for transfer to further processing means, e.g. tabletingequipment.

Alternatively, after rotation has been terminated, the IBC may beunloaded from the frame with its contents intact and then transferred toanother processing stage. Another alternative involves restoring the IBCto the FIG. 6 configuration and then adding a further component orcomponents to the IBC for mixing with the resident material in the IBCby further operation of the drive unit 106, again using the monitoringunit to monitor the mixing operation as described above. The mixingprocedure may involve supplementing the resident material in the IBCwith additional components in one or more stages, the IBC contents beingmonitored during each such stage and mixing being suspended onattainment of the desired mixing conditions (as detected by themonitoring means) during each stage while an additional component orcomponents are added. Once all components have been added and mixed tothe desired condition, the IBC is restored to the FIG. 6 configurationfor discharge of its contents or for removal (after lowering into theFIG. 5 position) and transfer to a further processing stage.

The staged mixing of components as described above may also be carriedout in the embodiment of FIGS. 1 and 2 and that of FIG. 3. In the caseof FIG. 3, the further component or components may be introduced atdifferent points along the length of the housing 50.

Although it is preferred to carry out monitoring non-invasively, i.e.without encroaching or interfering with the mixing process within themixing vessel, we do not exclude the possibility of monitoring unitdesigns which are invasive.

The mode of scanning is by diffuse reflection of the monitoringradiation. However, it will be appreciated that other scanning modes maybe used, such as reflectance techniques in which the radiation istransmitted to a reflective surface located within the mixing zone andthe reflected radiation is detected by the spectroscopic monitoringunit, or a technique in which the radiation is transmitted from onelocation and detection of the radiation is effected at a differentlocation. One embodiment utilising the latter technique is illustratedin FIG. 8 in which the radiation is routed through the interior of themixing vessel by means of a probe 130 which projects into the vesselthrough wall 132. The probe is composed of material suitable fortransmission of the radiation employed and, by means of reflectivesurfaces 134, 136 and recessed end face 138, defines a transmission pathcomprising an entry path 140, a interactive path 142 extending throughthe recess in the end face and hence through the interior of the mixingzone, and a return path 144. The radiation is directed to the probe 130from the AOTF or equivalent by optical fibre means 146 and is returnedto the detector of the monitoring means by optical fibre means 148, theoptical fibre means 146, 148 being provided on a support forming part ofthe monitoring means and which is brought into registration with theprobe 130 on mounting of the monitoring means on the vessel.

In the embodiment of FIGS. 4 to 7, the IBC is illustrateddiagrammatically. In practice, the IBC may be equipped with a frameworkto facilitate its handling, transport and coupling to the drive unit106. Such an arrangement is illustrated in FIGS. 9 and 10 to whichreference is now made. As shown, the framework comprises uprights 150located at the four corners of the IBC 100 and interconnected bycross-members 152, the IBC being mounted within the framework with itsoutlet located in spaced relation to the floor level. The framework maybe adapted for use with a fork lift to facilitate mounting on anddismounting from the drive unit 106. The lower ends of the uprights 150are provided with swivelling ground-engaging wheels 154 to facilitatemobility. At one side, the upper part of the IBC framework is providedwith a fitting 156 for coupling the IBC and its framework to the driveunit 106 in a substantially the same manner as illustrated in FIG. 7 sothat, in operation, the IBC is rotated about an oblique axis 156A (seeFIG. 10A) to secure an efficient tumbling action of its contents.

The monitoring unit M is mounted on one side of the IBC in registry witha viewing window 160 (e.g. a sapphire window) provided on the slopingwall 162 of the IBC to allow radiation transmission into the interior ofthe IBC. Mounting of the unit M is shown in more detail in FIG. 10. Theunit M comprises a housing 164 provided with handles H facilitatinghandling of the unit and heat dissipating fins 165 or the like forremoval of heat generated during operation of the unit. The housingaccommodates the various components described above in connection withFIGS. 1 and 2, including for example a spectroscopic monitoring unitsuch as Luminar 3030 AOFT spectroscopic equipment. The housing includesa window 166 through which outbound and inbound radiation can pass andwhich, when the housing 164 is mounted on the IBC, registers with thewindow 160. To this end, the IBC and associated framework is providedwith a mounting structure 168 to which the monitoring unit M can bereleasably secured.

The unit M includes a plate 170 in which the window 166 is providedwhich carries a number of releasable fastening devices 172 in the formof screwthreaded bolts which can be rotated by hand grips 174 and areintended to register with apertures in the mounting structure 168 forengagement with captive nuts 175. One edge 176 of the plate 170 forms alip which inserts into a locating channel defined between the mountingstructure 168 and a rebated member 178 secured to the mountingstructure. The unit M is assembled to the mounting structure 168 byinitially locating the lip 176 in the channel and, if necessary,positioning the unit M to register the fastening devices 172 with theassociated apertures and nuts 175. The fastening devices are thenoperated to firmly clamp the unit M in place for rotation with the IBCand its associated framework.

FIGS. 11 and 12 illustrate typical scans derived by the monitoring unitM during operation. FIG. 11 illustrates the time axis in the reversedirection with the more recent traces shown in the foreground. Thetraces T1 are scanned profiles which meet a predetermined criterion andare considered to be representative of the state of mixing, while tracesT2 are scanned profiles which correspond to free space. In practice, themonitoring unit M may process other profiles (not illustrated) which donot correspond lie between the two sets of traces T1 and T2 but areviews of free space and components of the mixture and hence are rejectedalong with traces T2. From FIG. 11, it will be seen that the traces T2gradually converge towards a static, substantially unchanging profilewhich may be indicate that the mixture has reached a certain state ofmixing, e.g. a homogeneous end point. In determining convergence,reference may be had to a specific part or parts of the spectroscopicprofiles, e.g. one or more wavelengths or wavelength rangescorresponding to the nature of the materials being mixed. For instance,the profiles may be analysed for convergence in a wavelength region orregions which correspond to the hydrocarbon content of the componentsundergoing mixing.

In prior PCT Application No. PCT/SE99/01325 there is disclosed apparatusfor and a method for mixing a plurality of materials to supply a mixturehaving a required homogeneity. The teachings in PCT Application No.PCT/SE99/01325 (the entire disclosure of which is incorporated herein bythis reference) relating to the management of the feed of mixed materialthrough a supply line are incorporated herein by this reference and areapplicable for example to the management of the mixed components afterexiting the mixing vessel.

Also, PCT/SE99/01325 describes the use of measuring devices formeasuring on-line, at at least one point in a supply line, thecomposition of the mixture passing through the supply line. Inaccordance with a further aspect of the present invention, the apparatusand method disclosed in PCT Application No. PCT/SE99/01325 may bemodified by employing measuring device(s) in the form of monitoringmeans as disclosed herein. Thus, for instance without being exhaustive,the measuring devices may each be in the form of a monitoring unithaving one or more of the following features:

detachable mounting as a unit (which may be self-powered and/orself-contained and/or portable) on the supply line;

communication with signal utilising means controlling the material feedand/or data acquisition means may be through a transmitter/receiverarrangement using radiative transmission, such as radio frequencysignals;

generation of the scanning radiation with the aid of an OATF asdescribed herein;

collection and storage of data within the monitoring means, preferablyusing a solid state memory device;

comparison of scanned profiles obtained at each location with a targetprofile stored locally within the monitoring unit, e.g. using solidstate memory; and

dockable with data acquisition and/or analysis means to allow datacollected by the monitoring means to be transferred to the dataacquisition and/or analysis means.

What is claimed is:
 1. A method of mixing a plurality of components,comprising: a) introducing components into a mixing vessel; b) mixingsaid components by rotating or oscillating the mixing vessel; and c)using a monitor to non-invasively monitor the contents of the vesselduring said mixing, said monitor collecting spectroscopic data, whereinsaid monitor rotates or oscillates with the mixing vessel.
 2. The methodof claim 1, wherein said mixing vessel has an axis of symmetry aboutwhich it is substantially symmetrical; and said mixing vessel is rotatedor oscillated about an axis that extends obliquely relative to said axisof symmetry.
 3. The method of claim 2, in which the vessel comprises anIntermediate Bulk Container (IBC).
 4. The method of claim 2, whereinsaid vessel is an Intermediate Bulk Container.
 5. The method of claim 1,further comprising generating at least one signal indicative of thestate of the contents of the vessel during mixing and modifying saidmixing in response to at least one signal.
 6. The method of claim 5,wherein said modification comprises discontinuing rotation oroscillation of the vessel.
 7. The method of claim 1, includingtransferring the data from the monitor to an off-board data storage or adata acquisition device during the mixing process.
 8. The method ofclaim 1, wherein said components include at least one pharmaceuticalcomponent.
 9. The method of claim 1, wherein said components include atleast one lubricant.
 10. The method of claim 1, wherein said monitorcomprises an acoustic optic tunable filter to produce, from a broad bandradiation source, radiation at a wide range of different wavelengthsand/or within different bands.
 11. A method of mixing a plurality ofcomponents, comprising: a) introducing components into a mixing vessel;b) mixing said components by rotating or oscillating the mixing vessel;c) non-invasively monitoring the contents of the vessel during saidmixing with a monitor that collects spectroscopic data, and d) storingsaid spectroscopic data on a data storage device, wherein said datastorage device is mounted on said oscillating or rotating mixing vessel.12. The method of claim 11, further comprising transferring said datafrom the data storage device to a data acquisition device after rotationor oscillation of the vessel has been discontinued.
 13. The method ofclaim 12, wherein, after rotation or oscillation of the vessel has beendiscontinued, the monitor is physically relocated to and docked with thedata acquisition device.
 14. An apparatus for mixing a plurality ofcomponents, comprising: a) a vessel for receiving the components, b) adrive means for rotating or oscillating the vessel about an axis toeffect mixing of the components within the vessel; and c) at least onespectroscopic monitor connected to the vessel for rotation oroscillation therewith, wherein said monitor is capable of obtaining datafor a spectroscopic profile as mixing proceeds.
 15. The apparatus ofclaim 14, further comprising an output signal to indicate that themixing process has reached a pre-set limit where modification of theprocess is necessary.
 16. The apparatus of claim 15, further comprisinga control device responsive to said output signal for controlling themixing process.
 17. The apparatus of claim 16, wherein said pre-setlimit is a predetermined condition derived from the spectroscopicprofile.
 18. The apparatus of claim 17, wherein in said predeterminedcondition is when the scanned profiles attain or converge towards asubstantially static state.
 19. The apparatus of claim 16, wherein saidcontrol of the mixing process includes terminating the mixing process.20. The apparatus of claim 14, further comprising at least one visual oraudible signal indicating a condition of the mixing.
 21. The apparatusof claim 14, further comprising a comparison device for comparing thespectroscopic profile obtained by the monitor to a target profile. 22.The apparatus of claim 21, wherein the comparison device is separatefrom the monitor and the vessel.
 23. The apparatus of claim 14, whereinthe monitor is self-powered.
 24. The apparatus of claim 14, wherein themonitor includes a data storage device for collecting data for transfer,during or, upon completion of a mixing cycle, to allow a record to bemaintained of each mixing cycle.
 25. The apparatus of claim 14, furtherincluding a signal transmitter mounted for movement with the vessel fortransmitting data to a remote receiver.
 26. The apparatus of claim 14,wherein the monitor is arranged to repeatedly collect data during eachcycle of rotation or oscillation of the vessel.
 27. The apparatus ofclaim 14, wherein the monitor is arranged to collect data substantiallycontinuously throughout each cycle of rotation or oscillation of thevessel.
 28. The apparatus of claim 14, further comprising a sensor todetermine the angular position of the vessel with respect to a datumposition.
 29. The apparatus of claim 14, wherein data is collected bythe monitor in dependence upon the rotational or angular position of thevessel with respect to the datum position.
 30. The apparatus of claim14, wherein the monitor emits radiation used for monitoring, and atleast a portion of the vessel is substantially transparent to at leastpart of said radiation.
 31. The apparatus of claim 30, wherein saidportion of the vessel is transparent to the radiation emitted from themonitor.
 32. The apparatus of claim 14, wherein the monitor is aself-contained unit releasably connected to the vessel.
 33. Theapparatus of claim 32, wherein the monitor is self-powered.
 34. Theapparatus of claim 33, wherein the self-contained unit comprises: a) amonitor; b) a radiative signal transmitter; and c) a compartment forreception of a battery for powering the unit.
 35. The apparatus of claim34, wherein the self-contained unit is adapted for docking at a locationin registry with the window through which spectroscopic data isobtained.
 36. The apparatus of claim 33, wherein the self-contained unitfurther comprises a data storage device comprising a microprocessor orcomputer forming part of the unit.
 37. The apparatus of claim 33,wherein the self-contained unit further comprises a profile-comparisondevice comprising a microprocessor or computer forming part of the unit.38. The apparatus of claim 14, further comprising a data acquisitiondevice for collecting scanning-derived data from the monitor.
 39. Theapparatus of claim 38, wherein the data acquisition device includes adocking station for receiving the monitor.
 40. The apparatus of claim14, further comprises a transmitter and remote receiver for use incontrolling the mixing process or for use in transferring data from themonitor to a data acquisition device.
 41. The apparatus of claim 14,wherein the mixing vessel is a V-blender.
 42. The apparatus of claim 14,wherein the mixing vessel is an Intermediate Bulk Container (IBC). 43.The apparatus of claim 14, wherein the monitor includes a near infra-redspectroscopic unit having a solid state tunable filter.
 44. An apparatusfor mixing a plurality of components, comprising: a) a mixer; b) atleast one spectroscopic monitor for repeatedly scanning the contents ofthe mixer to obtain and record data for use in monitoring changes in thespectroscopic profile; wherein the monitor is a portable unit adaptedfor detachable mounting on a wall of the mixer that, on completion ofthe mixing cycle, the monitor can be dismounted and transported to thedocking station c) a control device in communication with said at leastone spectroscopic monitor to control mixing; and d) a docking stationfor receiving said monitor and allowing transfer of data from themonitor to a data acquisition device.
 45. The apparatus of claim 44,wherein the mixer comprises at least one guide rail for mounting theportable unit in a desired position.
 46. The apparatus of claim 44,wherein the control device is provided with at least one handle.